Coumarins

1. WELCOME

2. CONTENTS COUMARINS CLASSIFICATION PSORALEN XANTHOTOXIN REFERNCES

3. COUMARINS Coumarin  (2H-chromen-2-one) is a fragrant organic chemical compound in the  benzopyrone  chemical class, which is a colorless crystalline substance in its standard state It is found naturally in many plants Families : umbelliferae , rutaceae , leguminaceae,etc Carribean word : coumarou

4. CLASSIFICATION  1. Simple coumarins , such as coumarin itself and dihydrocoumarin ,                                                            coumarin      dihydroxycoumarin

5. 2.Furocoumarins are formed in result of furan ring and coumarin condensation in 6,7 positions ( psoralen -derivatives) or 7,8 ( angelicin -derivatives). Substitutes may occur within any of these rings psoralen                        angelicin

6. 3. Pyranocoumarins are result of condensation of coumarin with 2’2’-dimethylpyrane in positions 5,6 ( dimethylxantyletin ); 6,7 or 7,8 ( visnadine ) and may have substitutes in any of rings.      2’2’dimethylxantyletin                     visnadin

7. 4.  Benzocoumarins containing benzyl ring condensed with coumarin in 3,4 positions occur   Anacardiaceae  and  Rosaceae .  Hydroxyderivative of 3,4-benzocoumarin is a structural component of ellagic acid. 3,4-benzocoumarin-hydroxy-derivative

8. PSORALEN

9. PSORALEN Synonym: Ficusin Parent compound in the family of furanocoumarins Umbeliferon derivative Linear furanocoumrin

10. BIOLOGICAL SOURCE Dried ripe fruits of psoralea corylifolia Family : Leguminosae Content of the fruit: Psoralen Isopsoralen It is present up to 3-4 % in the fruit

11. PSORALEA DERIVATIVES : imperatoxin xanthotoxin bergapten isomer : angelicin

12. SOLUBILITY: Very soluble in chloroform Less soluble in alcohol Sparingly soluble in ether Insoluble in petroleum ether

13. STRUCTURE Molecular formula :C 11 H 6 O 3

14. CONSTITUTION Structure of psoralen is deduced by using its degradation reaction It exhibits normal reactions of lactone of coumarin such as ring opening by alkali to give coumarinic acid or coumaric acid derivatives potassium permanganate causes oxidation of furan ring other oxidation produce furan 2,3-dicarboxylic acid

15. Dried fruits of Psoralea corylifolea Coarse powder To remove essential oils &resinous matter present on outer coat Defatted with petroleum ether Dried the marc

16. Extracted with methanol Methanolic extract ( psoralen +other coumarins + flavanoids ) Concentrate & dry Chromatographed on silica gel plate Chloroform as eluent Psoralen in first few fraction Crystallised from ethanol or solvent ether Concentrate to yield psoralen

17. IDENTIFICATION TESTS 1mg of psoralen in 5ml of ethanol+3 parts of propylene glycol+43 parts of water Blue fluoresence 1mg psoralen in 2ml ethanol+2 drops of 0.1M NaOH Emits yellow flourescence Uv light Uv light

18. 1mg of Psoralen in1ml of methanol Spotted on silicagel -G plates Plates are eluted in benzene:chloroform (98:2) Dried plates observed under UV light Psoralen shows blue fluracent spot with Rf value 0.25

19. USES In PUVA treatment for skin disease Psoriasis eczema vitiligo Recommended in the treatment of alopecia Psoralen is a mutagen & is used in molecular biology research Tannin activator in sun screens

20. SYNTHESIS

21. BIOSYNTHESIS

22. XANTHOTOXIN

23. XANTHOTOXIN Xanthotoxin or Methoxsalen is extracted from Ammi majus , a plant of the family Umbelliferae . It modifies the way skin cells receive the UV radiation. AMMI MAJUS - Bishops flower, Queen Anne’s Lace Also known as Bishopsweed , Bishop’s weed, Bullwort , Greater ammi , Lady’s lace, Laceflowe

24. Introduction contd… A tall plant originating in the Nile River Valley which has large, rounded, 10-15 cm flower heads made up of hundreds of tiny, snow-white florets. It is cultivated in North India also. The Seed of the plant contains Xanthotoxin

25. Chemistry Chemically, methoxsalen belongs to a class of organic natural molecules known as furanocoumarins . They consist of coumarin annulated with furan. Xanthotoxin is 8-methoxy psoralen or 8-methoxy 3’,2’-6,7 furocoumarin .

26. Chemistry contd…

27. Chemistry contd…

28. Extraction and Purification The pulverised coarse powder of the seed is used for extraction with n-hexane. Extraction is effected in 2-3 hrs and 3-4 washings are done. All the washings are combined and the solvent is distilled off. The separated solid is dried and de alkylated using HCl and methanol.

29. Extraction and Purification contd… The de alkylated material contains Xanthotoxol and Xanthotoxin The de alkylated material is refluxed with benzene for 2 hrs and cooled to room temp. Xanthotoxol is separated Xanthotoxin is crystallised from the filtrate at 10-15 C. .

30. Testing methods

31. SYNTHESIS

32. Synthesis contd…

33. Synthesis contd…

34. Synthesis contd… The activation of dimethylallyl pyrophosphate (DMAPP), produced via the mevalonate pathway, to form a carbo-cation via the cleavage of the diphosphates . Once activated, the enzyme umbelliferone 6-prenyltransferase catalyzes a C-alkylation between DMAPP and umbelliferone at the activated position ortho to the phenol, yielding demethylsuberosin . This is then followed by a hydroxylation catalyzed by the enzyme marmesin synthase to yield marmesin . Another hydroxylation is catalyzed by psoralen synthase to yield psoralen . A third hydroxylation by the enzyme psoralen 8-monooxygenase yields xanthotoxol which is followed by a methylation via the enzyme xanthotoxol O- methyltransferase and S- adenosyl methionine to yield methoxsalen

35. BIOLOGICAL ACTIONS Photosensitisation effect: when irradiated to long wave length UV radiation Killing bacteria: upon irradiation Formation of mutants: Mutagenic effect is seen in E Coli and Sarcina lutea Inactivation of tumour cells Inactivation of viruses

36. Properties and Uses Used to treat psoriasis, eczema, vitiligo , and some cutaneous Lymphomas in conjunction with exposing the skin to sunlight. Tonic, carminative and diuretic Relaxes smooth muscles Useful in kidney calculi and for angina pectoris In formulations of sun-tan lotions To increase the tolerance of sunlight

37. REFERNCES Pharmacognosy and pharmacobiotechnology by Ashutoshkar , revised expanded 2 nd edition Plant biosynthesis by Dr.S.S.Khadabadi , S.L.Deore , B.A.Baviskar Pharmacognosy & phytochemistry by Vinod.D.Rangari ,volume 2

38. THANK YOU